The multiplicity of cytochromes P-450 is being studied with monoclonal antibodies (MAbs) to 3-methylcholanthrene (MC)-induced rat liver cytochrome P-450. A semiquantitative, direct radioimmunoassay (RIA) has been developed to measure cytochrome P-450 in the microsomes from various tissues in animals that are untreated, or treated with MC. The amounts of cytochrome P-450 in different tissues and species, including human samples such as placentas and lymphocytes, were examined by competitive RIA. Individual differences have been observed by this method, which is more reliable than measurements of enzyme activity. Placentas from women who smoked cigarettes contained greater amounts of cytochrome P-450 with the MAb-specific epitope than placentas from nonsmokers. The amount of MAb-specific cytochrome P-450 in human peripheral lymphocytes increased after treatment with benz(a)anthracene. RIAs with multiple MAbs have also been used to detect epitope-specific cytochromes P-450 in animal livers, with the goal of classifying various tissues with respect to MAb-specific cytochromes P-450. Much higher levels of cytochrome P-450 recognized by MAb 1-7-1 were observed in MC-treated rats and C57BL/6 mice than in untreated rats, MC-treated DBA/2 mice and guinea pigs. These analyses provide an approach to the study of cytochrome P-450 multiplicity that is complementary to enzymatic and structural studies. RIA methods will aid in defining the epitope-specific cytochromes P-450 content in different tissues, species, and strains of laboratory animals, and in understanding the diversity of the cytochromes P-450 and their role in individual susceptibility to carcinogenesis.